Evidence map›Paper›PMID 40275070›Full record

ArticleLeukemia2025

ATM aberrations in chronic lymphocytic leukemia: del(11q) rather than ATM mutations is an adverse-prognostic biomarker.

Birna Thorvaldsdottir, Larry Mansouri, Lesley-Ann Sutton, Ferran Nadeu, Manja Meggendorfer, Helen Parker, Christian Brieghel, Stamatia Laidou, Riccardo Moia, Davide Rossi and 38 more

Abstract read
In one paragraph

Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

48 authors.

Birna Thorvaldsdottir *Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-7372-9925
Larry Mansouri *Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Lesley-Ann SuttonDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Ferran NadeuInstitut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.ORCID 0000-0003-2910-9440
Manja MeggendorferMLL Munich Leukemia Laboratory, Munich, Germany.
Helen ParkerCancer Genomics, School for Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Christian BrieghelDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0000-0002-1816-8106
Stamatia LaidouCentre for Research and Technology Hellas, Institute of Applied Biosciences, Thessaloniki, Greece.ORCID 0000-0002-4636-1579
Riccardo MoiaDivision of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.ORCID 0000-0001-7393-1138
Davide RossiClinic of Hematology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
Jana KotaskovaDepartment of Internal Medicine, Hematology & Oncology, University Hospital Brno, Brno, Czech Republic.ORCID 0000-0003-1672-7346
Julio DelgadoInstitut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.ORCID 0000-0002-5157-4376
Ana E Rodríguez-VicenteCancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.ORCID 0000-0001-6516-2172
Rocío BenitoCancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.ORCID 0000-0001-9781-4198
Gian Matteo RigolinHematology - Department of Medical Sciences, University of Ferrara, Ferrara, Italy.ORCID 0000-0002-8370-5190
Silvia BonfiglioIRCCS Ospedale San Raffaele, Milano, Italy.
Lydia ScarfòIRCCS Ospedale San Raffaele, Milano, Italy.ORCID 0000-0002-0844-0989
Mattias MattssonDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Zadie DavisMolecular Pathology Department, University Hospitals Dorset, Bournemouth, UK.ORCID 0000-0001-6959-4853
Panagiotis BaliakasDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-5634-7156
Inmaculada RapadoHospital Universitario 12 Octubre, Madrid, Spain.
Fatima MirasHospital Universitario 12 Octubre, Madrid, Spain.
Joaquín Martinez-LopezHospital Universitario 12 Octubre, Madrid, Spain.
Javier de la SernaHospital Universitario 12 Octubre, Madrid, Spain.
Jesús María Hernández RivasCancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.
María José LarráyozHematological Diseases Laboratory, CIMA LAB Diagnostics, University of Navarra, 31008 Pamplona, Spain, IdiSNA, Navarra Institute for Health Research, 31008, Pamplona, Spain.
María José CalasanzHematological Diseases Laboratory, CIMA LAB Diagnostics, University of Navarra, 31008 Pamplona, Spain, IdiSNA, Navarra Institute for Health Research, 31008, Pamplona, Spain.
Karin E SmedbyClinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Blanca EspinetMolecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain.ORCID 0000-0002-4294-8145
Anna PuiggrosMolecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
Lars BullingerDepartment of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Hum-boldt-Universität zu Berlin, Berlin, Germany.ORCID 0000-0002-5890-5510
Francesc BoschDepartment of Hematology, Hospital Universitari Vall d'Hebron (HUVH), Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0001-9241-2886
Bárbara Tazón-VegaDepartment of Hematology, Hospital Universitari Vall d'Hebron (HUVH), Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Fanny Baran-MarszakService d'hématologie biologique Hôpital Avicenne Assistance Publique des Hôpitaux de Paris Bobigny France, Bobigny, France.ORCID 0000-0002-3723-2927
David OscierMolecular Pathology Department, University Hospitals Dorset, Bournemouth, UK.ORCID 0000-0001-8486-2051
Florence Nguyen-KhacSorbonne Université, Service d'Hématologie Biologique, Hôpital Pitié-Salpêtrière, APHP, Paris, France.
Thorsten ZenzDepartment of Oncology and Haematology, University Hospital and University of Zurich, Zurich, Switzerland.ORCID 0000-0001-7890-9845
Maria Jose TerolDepartment of Hematology, INCLIVA Research Insitute, University of Valencia, Valencia, Spain.
Antonio CuneoHematology - Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
María Hernández-SánchezCancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.
Sarka PospisilovaDepartment of Internal Medicine, Hematology & Oncology, University Hospital Brno, Brno, Czech Republic.ORCID 0000-0001-7136-2680
Gianluca GaidanoDivision of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.ORCID 0000-0002-4681-0151
Carsten U NiemannDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0000-0001-9880-5242
Elias CampoInstitut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.ORCID 0000-0001-9850-9793
Jonathan C StreffordCancer Genomics, School for Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.ORCID 0000-0002-0972-2881
Paolo GhiaIRCCS Ospedale San Raffaele, Milano, Italy.ORCID 0000-0003-3750-7342
Kostas StamatopoulosCentre for Research and Technology Hellas, Institute of Applied Biosciences, Thessaloniki, Greece.ORCID 0000-0001-8529-640X
Richard RosenquistDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. richard.rosenquist@ki.se.ORCID 0000-0002-0211-8788

Funding

Cancer Research UK C34999/A18087
6 · The paper itself

Abstract

Despite the well-established adverse impact of del(11q) in chronic lymphocytic leukemia (CLL), the prognostic significance of somatic ATM mutations remains uncertain. We evaluated the effects of ATM aberrations (del(11q) and/or ATM mutations) on time-to-first-treatment (TTFT) in 3631 untreated patients with CLL, in the context of IGHV gene mutational status and mutations in nine CLL-related genes. ATM mutations were present in 246 cases (6.8%), frequently co-occurring with del(11q) (112/246 cases, 45.5%). ATM-mutated patients displayed a different spectrum of genetic abnormalities when comparing IGHV-mutated (M-CLL) and unmutated (U-CLL) cases: M-CLL was enriched for SF3B1 and NFKBIE mutations, whereas U-CLL showed mutual exclusivity with trisomy 12 and TP53 mutations. Isolated ATM mutations were rare, affecting 1.2% of Binet A patients and <1% of M-CLL cases. While univariable analysis revealed shorter TTFT for Binet A patients with any ATM aberration compared to ATM-wildtype, multivariable analysis identified only del(11q), trisomy 12, SF3B1, and EGR2 mutations as independent prognosticators of shorter TTFT among Binet A patients and within M-CLL and U-CLL subgroups. These findings highlight del(11q), and not ATM mutations, as a key biomarker of increased risk of early progression and need for therapy, particularly in otherwise indolent M-CLL, providing insights into risk-stratification and therapeutic decision-making.

Indexed as

Ataxia Telangiectasia Mutated ProteinsBiomarkers, TumorChromosome DeletionChromosomes, Human, Pair 11Leukemia, Lymphocytic, Chronic, B-CellMutationAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedPrognosisAtaxia Telangiectasia Mutated ProteinsATM protein, humanBiomarkers, Tumor

Identifiers

PMID40275070
PMCPMC12208880

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.